Lung Involvement Increases Relapse Risk in Chinese Patients With MPO-AAV, Study Says

Lung Involvement Increases Relapse Risk in Chinese Patients With MPO-AAV, Study Says
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Lung involvement increases the risk for both induction therapy resistance and disease relapse in ANCA-associated vasculitis (AAV) patients with autoantibodies against myeloperoxidase, a Chinese study suggests.

High levels of creatinine was also found to be a risk factor for treatment resistance.

These findings, while needing further confirmation, may help to identify high-risk patients and to optimize their disease management accordingly.

The study, “Risk factors for treatment resistance and relapse of Chinese patients with MPO-ANCA-associated vasculitis,” was published in the journal Clinical and Experimental Medicine.

AAV is a group of autoimmune diseases caused by the production of anti-neutrophil cytoplasmic autoantibodies (ANCAs), which mainly target one of two proteins — proteinase 3 (PR3) and myeloperoxidase (MPO) — in neutrophils, a type of immune cell. The neutrophils are wrongly activated and start destroying blood vessels, leading to swelling in different tissues and organs.

While some studies have worked on determining risk factors for treatment resistance and relapse after remission in AAV patients, the results remain inconclusive and, in some cases, conflicting. In addition, most of these studies analyzed Caucasian populations, which typically show different proportions of major AAV types compared to Asian populations.

In China, the dominant AAV type is microscopic polyangiitis (MPA), which is mainly associated with the production of MPO autoantibodies. It is unclear whether the potential predictors of treatment resistance and disease relapse in Caucasian populations are suitable for Chinese patients with AAV and MPO autoantibodies. Thus, a team of researchers in China set out to evaluate these risk factors in Chinese people with MPO-associated AAV, seen at a single tertiary medical center in China.

The researchers retrospectively analyzed the demographic and clinical data of 184 patients (100 men and 84 women) diagnosed with MPO-associated AAV from January 2009 to January 2018.

In terms of AAV types, most patients (91.85%) were classified as having MPA, eight (4.3%) as renal limited vasculitis, and seven (3.8%) as granulomatosis with polyangiitis. Patients’ mean age at diagnosis was 58.66 years, and they were followed for a median of 17.5 months (range between one month and 10 years).

The disease mainly affected the kidneys (95.1% of patients), followed by the lungs (59.2%), nervous system (23.4%), and the cardiovascular system (16.3%).

All patients received standard induction therapy — oral glucocorticoid prednisone combined with cyclophosphamide. Cyclophosphamide every three months or daily oral azathioprine or CellCept (mycophenolate mofetil) were given as maintenance treatment.

Results showed that 64 patients (34.9%) had resistance to induction therapy, which was significantly associated with the presence of lung involvement and high levels of creatinine (a marker for kidney disease) in the blood.

Having higher levels of platelets and C3 protein in the blood was associated with a lower risk of treatment resistance. C3 is a component of the immune complement system, and its excessive breakdown (and subsequently lower levels of C3) is associated with more severe AAV.

“The impact of [blood] creatinine level as a predictor for treatment resistance highlights the importance of early diagnosis and prompt commencement of immunosuppressive therapy,” the researchers wrote.

Of the 120 patients achieving remission with induction treatment, 29 (24.17%) experienced disease relapse, which was significantly associated with lung and cardiovascular involvement. Patients with high blood levels of globulins (a major type of protein) had a lower risk of disease relapse.

The researchers noted that the remission rates in these patients were lower than those reported for European and American populations, likely because all patients were positive for MPO autoantibodies — usually associated with poorer responses to immunosuppressive therapies.

The team also found that patients with treatment resistance or disease relapse were more likely to have their disease progress to end-stage renal disease and were less likely to survive.

The lack of an association between kidney dysfunction per se and treatment resistance or relapse may be associated with the low number of patients who underwent kidney biopsy (30.4%), the researchers noted.

Overall, the study’s findings suggest that lung involvement and high creatine levels are risk factors for treatment resistance, while the presence of lung or cardiovascular involvement increases the risk of disease relapse.

“Identifying patients at high risk of treatment resistance and relapse may aid in monitoring strategies and weighing the relative benefits of different treatment strategies,” the researchers wrote.

The team noted, however, that future larger studies are required to confirm these findings.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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